Some pyrrolobenzodiazepines (PBDs) have the ability to recognise and bond to specific sequences of DNA; the preferred sequence is PuGPu. The first PBD antitumour antibiotic, anthramycin, was discovered in 1965 (Leimgruber, et al., J. Am. Chem. Soc., 87, 5793–5795 (1965); Leimgruber, et al., J. Am. Chem. Soc., 87, 5791–5793 (1965)). Since then, a number of naturally occurring PBDs have been reported, and over 10 synthetic routes have been developed to a variety of analogues (Thurston, et al., Chem. Rev. 1994, 433–465 (1994)). PBDs are of the general structure:

They differ in the number, type and position of substituents, in both their aromatic A rings and pyrrolo C rings, and in the degree of saturation of the C ring. In the B-ring there is either an imine (N═C), a carbinolamine (NH—CH(OH)), or a carbinolamine methyl ether (NH—CH(OMe)) at the N10-C11 position which is the electrophilic centre responsible for alkylating DNA. All of the known natural products have an (S)-configuration at the chiral C11a position which provides them with a right-handed twist when viewed from the C ring towards the A ring. This gives them the appropriate three-dimensional shape for isohelicity within the minor groove of B-form DNA, leading to a snug fit at the binding site (Kohn, In Antibiotics III. Springer-Verlag, New York, pp. 3–11 (1975); Hurley and Needham-VanDevanter, Acc. Chem. Res., 19, 230–237 (1986)). Their ability to form an adduct in the minor groove, enables them to interfere with DNA processing, hence their use as antitumour agents.
In WO 00/12508, some of the present inventors disclosed the following compound (SJG-136, Compound 80):

This compound is also disclosed in Gregson, S. J., et al., Chem. Commun., 1999, 797–798. It has entered Phase I clinical trials in the UK and is likely to enter Phase I clinical trials in the US shortly.
One difficulty that this compound presents in formulation is that in water it converts to the di-carbinolamine form:
and when isolated often exists as a mixture of the imine, mono-carbinolamine and the di-carbinolamine forms. Furthermore, if the compound is isolated as a solid with a mixture of these three forms, the balance between them may change over time. Although this does not pose a problem for administration of the compound, it can provide difficulties in accurately assessing the amount of active substance in a given amount of powder.
SJG-136 does not appear to exhibit the cardiotoxicity that has been associated with pyrrolobenzodiazepines in the past.
Also disclosed in WO 00/12508, is the following compound (DRG-16, Compound 218):

This compound is also disclosed in Gregson, S. J., et al., J. Med. Chem., 2004, 1161–1174, in which it is shown to have similar properties to SJG-136.